The goal of this project is to elucidate the pathogenesis of feline leukemia virus (FeLV)-induced aplastic anemia in cats--a naturally occurring model of acquired potentially retrovirus-mediated aplastic anemia in humans. We seek to determine the viral genetic basis and pathobiologic mechanism whereby anemogenic feline retroviruses produce virus strain-specific ablation of bone marrow erythroid progenitor cells resulting in uniformly fatal aplastic anemia. The specific aims of the project are to: (1) determine the hemopoietic target cell on which anemogenic feline retrovirus exerts its major cytopathic effect; (2) identify the viral genetic determinants of hemopoietic cytopathicity and whether a consistent retrovirus variant or a consistent (clonal) integration site is associated with erythrocytopathogenicity; and (3) determine whether FeLV-induced aplastic anemia can be reversed by the combination antibody immunotherapy or antiviral chemotherapy coupled with allogeneic bone marrow transplantation. Methods being used to address these objectives are in vivo and in vitro biologic assay systems correlated with molecular analysis of the interactions of erythroablative FeLV with hemopoietic cells. An experimental in vivo system for rapid induction of aplastic anemia has been developed which employs specific-pathogen-free cats (inoculated initially with a biologically selected, serially passaged anemogenic FeLV isolate and presently with a molecularly cloned prototype anemogenic FeLV. A parallel in vitro experimental system employing clonigenic erythroid and myeloid progenitor cell colony growth is being used to assess retrovirus target cell specificity. The final objective is being addressed via a protocol we have derived for allogeneic bone marrow transplantation in which diseased, virus-infected hemopoietic stem cells are ablated with lethal (1000 rad) total body irradiation coupled with passive (FeLV antibody) immunotherapy to eliminate residual virus and shelter newly infused hemopoietic cells. (MI)